Schisandrol A Attenuates Myocardial Ischemia/Reperfusion‐Induced Myocardial Apoptosis through Upregulation of 14‐3‐3θ

Abstract

Schisandrol A (SA), one of the most abundant bioactive lignans extracted from the Schisandra chinensis (Turcz.) Baill., has multiple pharmacological properties. However, the underlying mechanisms of SA in protection against myocardial ischemia/reperfusion (MI/R) injury remain obscure. The present experiment was performed to explore the cardioprotective effects of SA in MI/R injury and hypoxia/reoxygenation- (H/R-) induced cardiomyocyte injury and clarify the potential underlying mechanisms. SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators. In the meantime, SA could profoundly ameliorate oxidative stress damage as evidenced by the higher glutathione peroxidase (GSH-Px) as well as lower malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, SA alleviated myocardial apoptosis as evidenced by a striking reduction of cleaved caspase-3 expression and increase of Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3θ. Mechanistically, SA prevented myocardial apoptosis through upregulating 14-3-3θ expression. Interestingly, siRNA against 14-3-3θ could promote apoptosis of cardiomyocytes, and H/R injury after knockdown of 14-3-3θ could further aggravate apoptosis, while overexpression of 14-3-3θ could significantly reduce apoptosis induced by H/R injury. Further, 14-3-3θ siRNA markedly weakened the antiapoptotic role of SA. Our results demonstrated that SA could exert apparent cardioprotection against MI/R injury and H/R injury, and potential mechanisms might be associated with inhibition of cardiomyocyte apoptosis at least partially through upregulation of 14-3-3θ.

Investigating the Mechanism of Action of Schisandra chinensis Combined with Coenzyme Q10 in the Treatment of Heart Failure Based on PI3K-AKT Pathway

“…After that, an animal model of isoproterenol-induced heart failure was successfully established. Numerous studies in the literature have shown that [9][10][11][12][13][14][15]18 mono-flavored S. chinensis as well as mono-flavored CQ10 can inhibit cardiomyocyte apoptosis and have a protective effect on cardiomyocytes. Based on this, this paper used S.chinensis in combination with CQ10 confirmed the ameliorative effect of S.chinensis in combination with CQ10 on isoproterenol-induced heart failure.…”

“…S. chinensis is a traditional northeastern authentic herb, mainly produced in Heilongjiang, Jilin, and Liaoning provinces, and is known as Schisandra because of its sweet, sour, and salty skin and pungent, bitter, and salty core. 8 Numerous experimental studies have shown that, [9][10][11][12][13][14][15] S.chinensis and its main chemical components schisandrin B, Schisanhenol, Schizandrin C and Schisandrol A can inhibit myocardial cell apoptosis, reduce myocardial cell inflammatory damage and have a cardioprotective effect.…”

Ginsenoside Rd promotes omentin secretion in adipose through TBK1-AMPK to improve mitochondrial biogenesis via WNT5A/Ca2+ pathways in heart failure

“…The protein concentration was calculated using a BCA protein assay kit (P0012, Beyotime, Shanghai, China) following the manufacturer's instructions [ 24 ]. Equal amounts of total protein (40 μg) were electrophoresed on 10% SDS-PAGE gels and transferred onto PVDF membranes.…”

Cardioprotective Potential of Berries of Schisandra chinensis Turcz. (Baill.), Their Components and Food Products

“…Recently, Gong et al [ 38 ] reported that schisandrin appears to attenuate myocardial ischemia/reperfusion-induced myocardial apoptosis through upregulation of 14-3-3 θ . The authors also noted that the tested compound has antioxidant properties: it increased the activity of GSH-PX and reduced the level of MDA and reactive oxygen species (ROS).…”